Zoledronic acid: an unending tale for an antiresorptive agent

被引：54

作者：

Caraglia, Michele ^{[1
]}

Marra, Monica ^{[1
]}

Naviglio, Silvio ^{[1
]}

Botti, Gerardo ^{[2
]}

Addeo, Raffaele ^{[3
]}

Abbruzzese, Alberto ^{[1
]}

机构：

[1] Univ Naples 2, Dept Biochem & Biophys, I-80138 Naples, Italy

[2] Fdn G Pascale, Ist Nazl Tumori, Pathol Unit, Naples, Italy

[3] S Giovanni Dio Hosp, UOC Oncol, Naples, Italy

来源：

EXPERT OPINION ON PHARMACOTHERAPY | 2010年 / 11卷 / 01期

关键词：

anticancer; breast cancer; Cyr61; cytotoxic drugs; metronomic; pharmacokinetic; prostate cancer; tipifarnib; zoledronic acid; DELTA-T-CELLS; ENDOTHELIAL GROWTH-FACTOR; ADVANCED BREAST-CANCER; LONG-TERM EFFICACY; PROSTATE-CANCER; BONE METASTASIS; SKELETAL COMPLICATIONS; MULTIPLE-MYELOMA; IN-VITRO; PREVENTIVE MEASURES;

D O I：

10.1517/14656560903485664

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Importance of the field: Therapy with zoledronic acid (ZOL) is a standard for patients with malignant bone disease. However, the antitumor effects of ZOL are demonstrated only in the preclinical setting and, therefore, they require pharmacological and molecular optimization. ZOL blocks protein isoprenylation, a pleiotropic and basic biochemical process within the cells regulating the activity of several proteins involved in survival and proliferating pathways. Areas covered in this review. The present review will cover different areas of research from pharmacology to cell biology and molecular biology regarding both direct and indirect anticancer effects of ZOL in humans. The challenge in demonstrating the clinical activity of ZOL is mainly based on its pharmacokinetic properties, which are discussed in detail. What the reader will gain: New data about the modes to overcome the limitations of ZOL and the following therapeutic strategies to implement its anticancer activity are described: i) development of pharmacological combinations; ii) finding of new molecular targets of ZOL; and iii) development of new pharmacological formulations of ZOL. Take home message: In conclusion, ZOL has still underestimated anticancer properties that require further investigation in both preclinical and clinical settings.

引用

页码：141 / 154

页数：14

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